Musculoskeletal injuries occur in a variety of settings including automobile crashes as well as in sports, recreation, and exercise (SRE). Participation in SRE is increasingly popular and widespread in American culture. The generally accepted view is that participation in SRE increases the risk of musculoskeletal joint injuries. The knee is the joint most frequently treated by orthopedic surgeons. Studies of people suffering knee ligament injuries have a significantly increased risk of generating a long-term, chronic disease such as osteoarthritis (OA). Each year approximately 80,000 knees suffer acute tears of the anterior cruciate ligament (ACL) in the U.S. alone; costing nearly $1 billion in health care costs. Surgical reconstruction of a torn ACL has not proven to significantly reduce the incidence of joint OA. Recent studies show that in more than 80% of ACL trauma cases, as for other knee ligament injuries, occult microcracks are diagnosed via magnetic resonance imaging of the traumatized joint in areas of bone underlying articular cartilage in the joint. While a significant effort has been initiated to investigate bone sequelae in the area of these 'bone bruises', relatively few studies have investigated the long-term consequences of the documented acute injury to cartilage overlying these occult microcracks. A hypothesis of the current proposal is that these occult microcracks result from excessive compressive overloading of the joint which, in part, causes rupture of the ACL in the human cadaver model. As such, these microcracks are an indication of acute injury to the overlying articular cartilage. A second hypothesis of the proposal is that this level of acute mechanical trauma may be sufficient to cause gross surface lesions and damage to articular cartilage with associated death of tissue cells, which correspondingly leads to joint OA in an animal model. A third hypothesis is that early pharmacological intervention into the traumatized joint with the surfactant P188, which targets repair of damaged cell membranes, will help delay, or even mitigate, the development of a post-traumatic OA in the joint. Then, surgical reconstruction of ruptured knee ligaments, such as the ACL, can stabilize the joint and lead to a satisfactory long-term outcome for this traumatized joint. [unreadable] [unreadable]